title: Polymer-filled microcontainers for oral delivery loaded using supercritical impregnation.
abstract: In the last years a large variety of drug delivery systems have been developed to improve bioavailability of therapeutics in oral administration. An increasing interest has arisen in reservoir-based microdevices designed for active ingredients like water insoluble compounds and fragile biomolecules. Such microdevices are designed to protect the active ingredient against degradation and deactivation, and to allow cytoadhesion and unidirectional drug release. There are few works which optimize the drug loading step and often therapeutics are dosed in the microdevices through laborious and time consuming procedures. This work proposes an effective loading technique for a poorly soluble model drug in microcontainers, by combining inkjet printing and supercritical fluid impregnation. Well defined quantities of poly(vinyl pyrrolidone) (PVP) solutions are dispensed into microcontainers by inkjet printing with a quasi-no-waste performance. Then ketoprofen is impregnated in the polymer matrix by using supercritical carbon dioxide (scCO2) as loading medium. The amount of polymer is controlled by the volume and the number of droplets of dispensed polymer and drug loading is tuned by varying the impregnation parameters. Compared to solid dispersions of the same drug and polymer, scCO2-impregnated microcontainers exhibit a more reproducible drug loading and a faster dissolution rate of the active compound which allows drug release to be modulated. The combination of these loading techniques potentially allows the high throughput fabrication of microdevices for oral drug delivery with a safe and solvent-free solution.
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark, Kongens Lyngby 2800, Denmark. Electronic address: paom@nanotech.dtu.dk.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marizza
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark, Kongens Lyngby 2800, Denmark.
authors.forename: Stephan S
authors.initials: SS
authors.lastname: Keller
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark, Kongens Lyngby 2800, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Boisen
mesh_terms: D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002245:Carbon Dioxide / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D007660:Ketoprofen / Q000008:administration & dosage*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002245:Carbon Dioxide; D007660:Ketoprofen; D011205:Povidone
keywords: Drug delivery; Ketoprofen; Microcontainer; PVP; Poorly soluble drugs; Supercritical fluids